G-proteincoupledreceptors(GPCRs)transduceavarietyofsignalsfromtheextracellularenvironmentacrosstheplasmamembrane.OneofthecommonsignalingsystemsutilizedbyGPCRsactivatesproteinkinaseC(PKC),aubiquitousfamilyofserine/threonineproteinkinases.ThepathwayleADIngtoPKCactivationstartswithaclassofGPCRsthatinteractwithandactivateGqG-proteinswhenthereceptorhasagoNISTligandbound.GPCRsthatactthroughGqincludesomemuscarinicacetylcholinereceptors,manypeptidereceptors,andthe5-HT2SEROtoninreceptors.ActivatedGqwithGTPboundactivatesitsdownstreamtargetphospholipaseC(PLC)tohydrolyzethemembranelipidPIP2,producingIP3anddiacylglycerol(DAG).IP3iswater-solubleanddiffusesthroughthecytoplasmtotheER,whereitbindstoandopensacalciumchannel,releasingcalciumstoresfrominsidetheERintothecytoplasm.Calciumaltersmanycellularprocesses,inpartbybindingtoregulatoryproteinssuchascalmodulinandcalcineurin.TheinteractionofbothDAGandcalciumwithPKCactivatesitskinaseactivityandthephosphorylationofmanydifferentproteintargetsalterstheiractivity.TheinvolvementofPKCincellularproliferationandthecellcycleisindicatedbytheactivityoftumorpromoterslikephorbolestersasPKCactivators. Contributor:GlennCroston,PhD REFERENCES: